The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV-infected people who have never received anti-HIV therapy be treated with a triple drug regimen. The most commonly prescribed and successful regimen contains the medication efavirenz (EFV). However, this regimen has been shown to cause undesirable side effects for some patients and is therefore not an option for them. Alternative regimens are needed for these patients.

The main study will look at how well different combinations of anti-HIV drugs work to decrease the amount of HIV in the blood (viral load) of and allow immune system recovery in people who have never received anti-HIV therapy. It will also examine drug tolerability and safety for the various drug combinations.

This substudy of A5257 will further examine the effects of these new regimens on metabolic, skeletal, and cardiovascular factors.

Of the five anti-HIV drug classes, three are recommended as first-line regimens for patients who have never received anti-HIV treatment before (treatment naive): nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). The U.S. Department of Health and Human Services (HHS) guidelines recommend that treatment-naive HIV- infected people be treated with a triple drug regimen that includes two NRTIs + one NNRTI or two NRTIs + one PI as their initial treatment regimen.

According to data, an efavirenz (EFV)-containing regimen (two NRTIs + one NNRTI, with EFV as the NNRTI) requires fewer pills for the patient, has mild and few side effects, and is more effective in reducing viral load than other regimens, making it the preferred choice for most patients. However, for some patients, an EFV-containing regimen is not possible due to dangerous side effects, acquired NNRTI-resistant HIV virus, or other undesirable effects. For these patients, it is necessary to find alternative regimens with comparable safety and efficacy. The main study will examine how well different combinations of anti-HIV drugs work, including safety and drug tolerability for various combinations.

Some participants of A5257 will be asked to participate in this optional metabolic substudy of A5257. It will only take place at some study sites and may last up to 144 weeks, including time on A5257. The primary focus of this substudy is to examine carotid artery intima-media thickness (CIMT) as it relates to both ritonavir (RTV)- and raltegravir (RAL)-containing regimens. Randomization, stratification, treatment assignments, and study visits will be as per A5257. Female participants who become pregnant while in the study must inform the study staff immediately, and will subsequently be discontinued from the study without any further evaluations.

In the first 10 participant at each imaging site, the flow-mediated vasodilation (FMD) test, which measures cardiovascular risk, will be completed twice. This test will be performed on Week 24.

The need for this substudy stems from data showing an increasing number of HIV -infected patients with metabolic, skeletal, and cardiovascular diseases, which may be directly related to the effects of antiretroviral therapy. Conventional understanding of disease development, risk factors, and consequences pertain to persons receiving older antiretroviral drugs. Consequently, it is necessary to examine the impact of newer antiretroviral drugs on metabolic, skeletal, and cardiovascular factors. The purpose of this substudy is to understand the contributions of HIV disease-related factors and antiretroviral therapy to the development of metabolic, skeletal, and cardiovascular disease among HIV -infected patients.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

HIV-infected participants currently enrolled in study A5257

Criteria

Inclusion Criteria:

Enrollment in A5257 and intent to enroll in A5001 (ALLRT)

Signed informed consent

Participating in research at any AIDS Clinical Trial Group (ACTG) clinical research site or select International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group sites

Uncontrolled hypothyroidism or hyperthyroidism which in the opinion of the site investigator would affect substudy participation

Current use of statins, fish oil (less than 2 grams per day), fibric acid derivatives, or niacin (more than 1000 mg per day) (NOTE: Current use of fish oil and niacin is defined as receiving treatment in the 8 weeks before study entry)

Intention to start pharmacological or surgical intervention for weight loss

Use of any ART in the 30 days before study entry

Presence of decompensated cirrhosis

Pregnant or breastfeeding

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00851799